A physiologically relevant hyperthermia selectively activates constitutive hsp70 in H9c2 cardiac myoblasts and confers oxidative protection.

Abstract

Whole body hyperthermia (42-43 degrees C for 15-20 min) elicits the formation of heat shock proteins (hsps) and improves cardiac recovery from subsequent ischemia/reperfusion. However, the beneficial effects of this response are compromised by initial tissue injury, which limits its clinical applicability. Using a simplified myocardial model (rat heart-derived H9c2 myoblasts) a hypothesis was tested that chronic, mild hyperthermia is as effective as acute heat shock in inducing the heat shock response. Our results indicate that 39 degrees C pre-conditioning evoked thermotolerance and oxidative resistance, but caused no detectable adverse effects. An improved survival after hydrogen peroxide (H2O2) exposure (40-54 microm for 3 h) was first observed in cells pre-conditioned at 39 degrees C for 24 h. As the duration of thermal pre-incubation increased, cells became more resistant than the control (37 degrees C) to a greater toxicity of H2O2(68 microm). An optimal oxidative protection developed by;4 days at 39 degrees C and this persisted for as long as the cells were incubated at this temperature. Three hsps are known to modulate cellular antioxidant defenses: the constitutive-hsp70 (hsc70), its inducible counterpart (hsp70), and hsp27. The authors found that mild hyperthermia selectively induced only hsc70, which demonstrates a lower temperature threshold for activation of hsc70. The initial protection against the milder H2O2challenge correlated with a homogenous distribution of pre-existing hsc70. The subsequent optimal protection was associated with an identical distribution pattern and a moderate increase of hsc70. These observations suggest that mild hyperthermia induces a beneficial adaptive response, in which hsc70 plays a critical role.